XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells
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Ploegh_XBP-1 regulates.pdf
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Author(s)
Hu, Chih-Chi Andrew
Dougan, Stephanie K.
McGehee, Annette M.
Ploegh, Hidde
Love, John C
Date Issued
April 2009
Journal
EMBO Journal
Publisher
Nature Publishing Group
Citation
Hu, Chih-Chi Andrew et al. “XBP-1 Regulates Signal Transduction, Transcription Factors and Bone Marrow Colonization in B Cells.” The EMBO Journal 28.11 (2009): 1624–1636. © 2012 European Molecular Biology Organization
Version
Final published version
Abstract
XBP-1, a transcription factor that drives the unfolded protein response (UPR), is activated in B cells when they differentiate to plasma cells. Here, we show that in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is induced normally on induction of differentiation, suggesting that activation of XBP-1 in B cells is a differentiation-dependent event, but not the result of a UPR caused by the abundant synthesis of secreted IgM. Without XBP-1, B cells fail to signal effectively through the B-cell receptor. The signalling defects lead to aberrant expression of the plasma cell transcription factors IRF4 and Blimp-1, and altered levels of activation-induced cytidine deaminase and sphingosine-1-phosphate receptor. Using XBP-1-deficient/Blimp-1-GFP transgenic mice, we find that XBP-1-deficient B cells form antibody-secreting plasmablasts in response to initial immunization; however, these plasmablasts respond ineffectively to CXCL12. They fail to colonize the bone marrow and do not sustain antibody production. These findings define the role of XBP-1 in normal plasma cell development and have implications for management of B-cell malignancies.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1038/emboj.2009.117
